Objective To observe the value of non-contrast CT radiomics extreme gradient boosting(XGBoost)model based on SHAP method for predicting acute necrotic collection(ANC)around acute pancreatitis(AP).Methods A total of 307 patients with initially clinically diagnosed AP were retrospectively enrolled.The optimal radiomics features of peripheral pancreatic tissue volume of interest(VOI)were extracted and screened based on automatic segmentation on the first non-contrast CT,and the evaluation results of modified CT severity index(MCTSI)score of AP severity based on first enhanced CT were recorded.The patients were divided into peripancreatic ANC group(ANC group)and acute peripancreatic fluid collection(APFC)group according to follow-up abdominal CT.XGBoost method was used to construct radiomics model,MCTSI model and combined model for predicting AP ANC based on the optimal radiomics features,MCTSI and their combination,respectively.The diagnostic efficacy of each model was evaluated using 5-fold cross-validation method,and the contribution of each variable to combined model was analyzed with SHAP method.Results Among 307 cases,there were 134 cases in ANC group and 173 in APFC group.Totally 6 optimal radiomics features were screened based on the first non-contrast CT.The area under the receiver operating characteristic curve(AUC)of radiomics model,MCTSI model and combined model was 0.936,0.693 and 0.917,respectively.The AUC of MCTSI model was lower than that of radiomics model and combined model(Z=-3.485,-2.824,both P＜0.01),while no significant difference of AUC was found between radiomics model and combined model(Z=-0.817,P=0.415).The contribution of optimal radiomics features to combined model were all higher than that of MCTSI score.Conclusion Non-contrast CT radiomics XGBoost model could effectively predict AP ANC.

Objective To observe the value of non-contrast CT radiomics extreme gradient boosting(XGBoost)model based on SHAP method for predicting acute necrotic collection(ANC)around acute pancreatitis(AP).Methods A total of 307 patients with initially clinically diagnosed AP were retrospectively enrolled.The optimal radiomics features of peripheral pancreatic tissue volume of interest(VOI)were extracted and screened based on automatic segmentation on the first non-contrast CT,and the evaluation results of modified CT severity index(MCTSI)score of AP severity based on first enhanced CT were recorded.The patients were divided into peripancreatic ANC group(ANC group)and acute peripancreatic fluid collection(APFC)group according to follow-up abdominal CT.XGBoost method was used to construct radiomics model,MCTSI model and combined model for predicting AP ANC based on the optimal radiomics features,MCTSI and their combination,respectively.The diagnostic efficacy of each model was evaluated using 5-fold cross-validation method,and the contribution of each variable to combined model was analyzed with SHAP method.Results Among 307 cases,there were 134 cases in ANC group and 173 in APFC group.Totally 6 optimal radiomics features were screened based on the first non-contrast CT.The area under the receiver operating characteristic curve(AUC)of radiomics model,MCTSI model and combined model was 0.936,0.693 and 0.917,respectively.The AUC of MCTSI model was lower than that of radiomics model and combined model(Z=-3.485,-2.824,both P＜0.01),while no significant difference of AUC was found between radiomics model and combined model(Z=-0.817,P=0.415).The contribution of optimal radiomics features to combined model were all higher than that of MCTSI score.Conclusion Non-contrast CT radiomics XGBoost model could effectively predict AP ANC.

Objective To explore the enzymatic reaction kinetics of metoprolol tartrate in an in vitro human liver microsome incubation experiment and to explore the effect of famotidine on the metabolism of metoprolol tartrate.Methods An LC-MS/MS method was developed to accurately measure the concentration of metoprolol tartrate in a human liver microsomal incubation system.A human liver microsome incubation system was established to determine the optimal incubation time and protein concentration;using the substrate depletion method,the enzymatic reaction kinetics parameters of metoprolol tartrate(such as Vmax and Km).Series concentrations of famotidine were co-incubated with metoprolol tartrate,and the concentration of metoprolol tartrate was measured to evaluate the effect of famotidine on its metabolism.Results The optimal incubation time for metoprolol tartrate in human liver microsomes was found to be 60 minutes,with an optimal protein concentration of 1.0 mg/mL.The enzymatic reaction kinetics parameters were Vmax=0.07 μmol/min/mg protein and Km=7.84 μmol/L.Conclusion The results indicated that famotidine did not produce a significant inhibitory effect on the metabolism of metoprolol tartrate in human liver microsome incubation system,suggesting that the combination of these two drugs may be relatively safe.

Chimeric antigen receptor T (CAR-T) cell therapy achieved advanced progress in the treatment of hematological tumors. However, the application of CAR-T cell therapy for solid tumors still faces many challenges. Competition with tumor cells for metabolic resources in an already nutrient-poor tumor microenvironment is a major contributing cause to CAR-T cell therapy’s low effectiveness. Abnormal metabolic processes are now acknowledged to shape the tumor microenvironment, which is characterized by increased interstitial fluid pressure, low pH level, hypoxia, accumulation of immunosuppressive metabolites, and mitochondrial dysfunction. These factors are important contributors to restriction of T cell proliferation, cytokine release, and suppression of tumor cell-killing ability. This review provides an overview of how different metabolites regulate T cell activity, analyzes the current dilemmas, and proposes key strategies to reestablish the CAR-T cell therapy’s effectiveness through targeting metabolism, with the aim of providing new strategies to surmount the obstacle in the way of solid tumor CAR-T cell treatment.

OBJECTIVE： To provide reference for the evaluation of the correlation between drugs and adverse drug reaction （ADR） and the implementation of medication therapy management （MTM）. METHODS： Clinical information of a elderly patient with chronic disease （hypertension and coronary heart disease） whose suffered from leukocyte and platelet counts reduction and abnormal liver biochemical examination after taking candesartan were analyzed retrospectively in outpatient department of Tianjin Third Central Hospital. MTM pharmacists analyzed the correlation of candesartan with ADR using Naranjo evaluation scale method. The reasons for abnormal liver biochemical examination were analyzed by Naranjo evaluation scale method combined with Roussel Uclaf causality analysis method （called RUCAM method for short）. The medication reconciliation was conducted according to the results， and pharmacists cooperated with doctors to set individualized medication regimen and follow-up. RESULTS： By Naranjo evaluation scale method， analysis results showed that candesartan was “probably related” to ADR. By RUCAM method， analysis results showed that candesartan was “probably related” to liver biochemical abnormalities. MTM pharmacists suggested that candesartan should be stopped in time and the patient’s medication should be adjusted. The physician and the patient adopted the pharmacist’s advice. After 38 days of drug withdrawal， the patient’s ADR symptoms disappeared， and leukocyte count， platelet count and liver biochemical examination were normal. After adjustment of medication， the patient was followed up for 6 months with normal blood pressure. CONCLUSIONS： Naranjo evaluation scale method and RUCAM are simple and feasible in evaluating the correlation of drugs with ADR and hepatotoxicity. The two methods are consistent in evaluating the correlation between drugs and hepatotoxicity. Naranjo scale method and RUCAM method can be combined to analyze the correlation between drugs and ADR with abnormal liver biochemical examination.

Objective To evaluate the sensitivity and specificity of enzyme assays,and to provide disease spectrum of lysosomal storage diseases (LSDs).Methods Three thousand three hundred and sixty-four high risk individuals were screened for 24 LSDs at Guangzhou Women and Children's Medical Center between January 2009 and December 2016.Twenty-two kinds of enzyme activities from peripheral blood leucocytes or plasma were measured by using the fluorometry or colorimetry of corresponding artificial substrates,screening for 24 LSDs diseases.Measurement data were represented by (x) ± s,and count data were expressed as a percentage or composition ratio.Results A total of 283 subjects were diagnosed with 18 different kinds of LSDs,and the positive rate of high-risk screening was 8.4％.Among the identified patients,172 cases (60.8％) were mucopolysaccharidosis (MPS),79 cases (27.9％) were sphingolipidoses,18 cases (6.4％) were Pompe diseases,10 cases (3.5％) were affected with mucolipidoses,3 cases (1.1％) were glycoprotein storage diseases,and 1 case(0.4％) was Wolman disease.Of the MPS cases,there were 75 cases of MPS Ⅱ (43.6％),45 cases of MP5 ⅣA (26.2％),24 cases of MPS Ⅵ (14.0％) and 20 cases of MPS Ⅰ (11.6％).Gaucher disease (23/79 cases,29.1％) and metachromatic leukodystrophy (MLD) (21/79 cases,26.6％) were common in sphingolipidoses group.Both the sensitivity and specificity of enzyme assays on peripheral blood leucocytes for LSDs were 100％.Conclusions The most common kinds of LSDs are MPS Ⅱ,MPS Ⅳ A,MPS Ⅵ,Gaucher disease,MLD and Pompe disease.Leukocyte enzymology analysis of high-risk screening LSDs has high sensitivity and specificity.

Objective To study the application of walking combined with Buerger exercise in the treatment of grade 0 diabetic foot.Methods Eighty patients with grade 0 diabetic foot were randomly divided into observation group and control group.The control group was trained by walking exercise .The observation group was trained by walking combined with Buerger exercise through 12 months of training.The changes of self-sensory symptoms,ABI and DAWV were observed.Results The self-sensory symptoms of the two groups were significantly decreased (observation group: markedly effective 15 cases,effective 19 cases;control group: markedly effective 5 cases,effective 23 cases).The effective rate of the observation group was higher than that of the control group (85% vs.70%,χ2 =7.831,P <0.05).The ABI ratio of the two groups were higher than those before treatment ,and the ABI ratio of the observation group was higher than that of the control group [(0.889 ±0.113) vs.(0.842 ±0.124),t =1.772 P <0.05].The ratio of DAWV in the observation group was higher than that in the control group [(6.772 ±0.435)cm/s vs.(6.543 ±0.552)cm/s,t =2.061,P <0.05].Conclusion Walking combined with Buerger exercise can improve the blood flow velocity and blood flow of the collateral circulation of the lower limbs of patients with grade 0 diabetic foot,and improve the self-sensory symptoms of peripheral neuropathy .

Objective To investigate the application of resistive exercise combined with Buerger exercise in lower extremity vascular disease of type 2 diabetes mellitus .Methods According to the order of admission ,120 type 2 diabetes mellitus patients with lower extremity vascular disease were randomly divided into resistance exercise group ,Buerger exercise group and combined exercise group ,with 40 cases in each group .The resistance exercise group was given resistance exercise ,the Buerger exercise group was given Buerger exercise ,and the combined exercise group was given resistance exercise combined with Buerger movement .The changes of self -inductance ,ABI and DAWV of the three groups were observed .Results The clinical symptoms of the three groups were significantly reduced ( the resistance exercise group:markedly effective in 10 cases,effective in 14 cases;the Burger exercise group:markedly effective in 15 cases,effective in 17 cases;the combined exercise group: markedly effective in 22 cases,effective in 13 cases),the effective rate of the combined exercise group was higher than that of the resistance exercise group and Buerger exercise group ( the resistance exercise group:60.0％;the Burger exercise group:80.0％;the combined exercise group:87.5％,χ2 =11.333,P <0.05).The ABI of the three groups were higher than those before treatment,and the ABI ratio of the combined exercise group [(0.933 ±0.113)]was higher than that of the resistance exercise group[(0.866 ±0.112)] and the Buerger exercise group[(0.888 ±0.111)](t=1.796,2.663,all P<0.05 ) .The DAWV of the three groups increased compared with those before treatment , and the DAWV of the combined exercise group[(7.023 ±0.535)cm/s]was higher than that of the resistance exercise group [(6.633 ± 0.552)cm/s] and the Buerger exercise group [(6.772 ±0.435) cm/s] (t =2.302,3.209,all P <0.05). Conclusion Resistant exercise combined with Buerger exercise is helpful to improve the blood flow velocity and blood flow in the lower extremity vessel of patients with diabetic lower limb vascular disease , and can improve the self-sensitization symptoms of peripheral neuropathy in patients .

AIM:TostudythefunctionofmicroRNA(miR)-19aandmiR-92abyseed-targetinginhibitionin multiple myeloma cells and their signal pathways .METHODS:The experiments were divided into t-antimiR-19a group, t-antimiR-92a group, scramble control group and blank control group .The growth-inhibitory potencies were measured by MTT assay.The ability of cell colony formation was measured by cell colony formation assay .The ability of cell invasion was measured by Transwell experiment .The miR-19a and miR-92a target gene signal pathways were integrated by miRFo-cus software.RESULTS:MTT assay showed that t-antimiR-19a and t-antimiR-92a significantly inhibited the viability of multiple myeloma cells , and the best concentration and time were 0.5μmol/L and 48 h, respectively .The colony number in t-antimiR-19a/92a group was less than that in scramble control group .The transfection with t-antimiR-19a or t-antimiR-92a effectively decreased the cell invasion , as the relative invasion cell number was significantly decreased compared with scramble control group.miR-19a and miR-92a were involved in mTOR signaling, cell cycle and other cancer pathways . CONCLUSION:miR-19a and miR-92a cluster might be a potential target for therapeutic intervention in multiple myelo-ma.

Objective To analyze the relationships and differences of the clin(HFMD) ical signs and the possibility of children with herpangina developing into HFMD by observing the clinical signs.Methods Eighty children diagnosed herpangina clinically firstly were divided into Group A,B and C.Group A included 42 cases with only herpangina,and Group B including 28 cases who were herpangina developing into mild HFMD and Group C including 10 cases with serve HFMD.The clinical signs of the three groups,including blood routine test and lymphocyte count,neutrophil count,and monitor the degree of fever,blood pressure,heart rate,respiratory and digestive system,nervous system symptoms were recorded.Results In Group A,B and C,white blood cell number,lymphocyte number,neutrophil number were no significant difference(P ＞ 0.05).However,fever degree,thermal history,heart rate,respiratory rate,systolic pressure,diastolic pressure were significant differences (F =5.03,3.62,4.83,3.65,6.72,3.74 ; P ＜ 0.05).Meanwhile The sigh of loss of appetite,vomiting,diarrhea,gastrointestinal symptoms and easily frightened,limb jitter,sleepiness were statistically significant(x2 =6.10,5.75,4.86,3.58,3.42,4.35;P ＜0.05).Conclusion The herpangina children with symptoms and signs such as higher fever and higher blood pressure,simultaneously with diarrhea,vomiting,hyperarousal and amyostasia,have the more chance to develop HFMD.